Bisphosphonates for periprosthetic bone loss after joint arthroplasty: a meta-analysis of 14 randomized controlled trials

The present meta-analysis aimed to evaluate the middle-term efficacy of bisphosphonates on maintaining periprosthetic bone mass after joint arthroplasty and the potential influential factors. It was found that the protective effect of bisphosphonates, probably modified by its generation and the prosthesis location, could persist in a middle-term follow-up after surgery and after drug discontinuation. A previous meta-analysis of 6 RCTs with follow-up of 12 months suggested that bisphosphonates (BPs) could prevent bone loss after arthroplasty up to 6 months. Our meta-analysis based on 14 RCTs involving 671 patients with follow-up up to 72 months aimed to evaluate the middle-term efficacy of BPs, understand the sources of heterogeneity, and comprehensively identify the potential influential factors. Electronic databases searching and hand searching of conference proceedings were conducted. We evaluated the methodological quality and abstracted relevant data. With fixed effect model we calculated the weighted mean differences to evaluate bone mineral density at different time points. We also conducted a systematic review for BP-related adverse effects. The significantly less periprosthetic bone loss occurred in the BP-treated group than in the control group at 3, 6, and 12 months, and between 24 and 72 months after the index surgery. The protective effect persisted during 18 to 70 months after discontinuation of BPs. The heterogeneity was minimized with the separation of hip and knee trials during the analysis. The efficacy was more potent for the second and the third generation of BPs than the first generation. None of the trials noted serious or fatal adverse effects related to BPs. The overall moderate evidence from the RCTs confirmed the significantly short-term and middle-term efficacy of BPs on periprosthetic bone loss after joint arthroplasty. To obtain a better efficacy, the second and the third generation of BPs may be the choice.